The continuing goal of this project is to develop methods to evaluate environmental mammary carcinogens, and to define factors and mechanisms related to susceptibility to mammary cancer. In this renewal we will continue to develop and evaluate both direct and mediated rat mammary cell mutagenesis sytems. These mutagenesis systems, together with the quantitation of B(a)P- and DMBA-DNA adduct formation and removal as well as metabolism, will be used to: 1) compare the interaction of DMBA and B(a)P with mammary cells in vivo and in vitro; and 2) delineate the relationship of these parameters and susceptibility to induced breast cancer in two rat models. The rat models include one in which Sprague-Dawley rats, which are highly susceptible to PAH-induced mammary cancer, will be compared to Long Evans rats, which are less susceptible. The second rat model will compare virgin Sprague-Dawley rats (susceptible to PAH-induced mammary carcinogenesis) to mid-pregnant Sprague-Dawley rats (relatively resistant). This project may produce model systems and information that may ultimately lead to the lowering of the morbidity and mortality of breast cancer, the major lethal cancer of women.